Acquisition of a linear Q-Trap LC/MS/MS System: Funds are requested from the Division of Research Resources for the purchase of an Applied Biosystems Q-Trap Pro LC/MS/MS system. Until the development of this instrument, 3-Dimensional (3-D) ion traps were all that have been available for proteomics research. Although 3-D ion traps have been extremely useful, they suffer form several disadvantages for proteomics research. Mass accuracy is poor, which sometimes results in ambiguous database search results. Important low mass ions are not observed in typical MS/MS experiments. It is possible to increase resolution by using longer cycle times. However, this results in a significant decrease in sensitivity. Finally, true precursor ion and neutral loss scans, which are useful for protein characterization, are not available. The linear (or 2- Dimensional) ion trap has enhanced resolution and mass accuracy compared to conventional 3-D ion trap and standard triple quadrupole mass spectrometers, which provides greater confidence in database search results. Furthermore, superior full-scan sensitivity in MS and MS/MS modes permits analysis of important low-copy proteins. The Q-Trap instrument provides standard triple quadrupole-like MS/MS fragmentation patterns with no low mass cutoff. This provides better peptide sequence coverage, and so also improves database searching. Unique scan functions are also available on the linear Q-Trap system when compared with the conventional 3- D ion trap. This allows a series of sophisticated MS/MS experiments (such as precursor ion and constant neutral loss scans) to be conducted during a single LC/MS run and so significantly enhances throughput when conducting protein identification experiments. The Enhanced Multiply Charged (EMC) scan is particularly useful as it eliminates the majority of singly charged ions, which in turn, maximizes the signal-to-noise ratio for multiply charged ions. A major user group consisting of four NIH-funded investigators would use the instrument to perform proteomics research. A minor user group consisting of six NIH-funded investigators would also conduct proteomics research using the instrument. An occasional user group of eight NIH-funded investigators would use the instrument for most of the remaining instrument time. It is estimated that over five years, the instrument would benefit the research programs of an additional 20-30 investigators. Therefore, the new instrument would impact significantly on research programs of some 38-48 NIH-funded investigators at the University of Pennsylvania.